Browse
Submit Data
Databases
API
Help

Dataset Information

23 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Selective dependence on IL-7 for antigen-specific CD8 T cell responses during airway influenza infection.

ABSTRACT: Interleukin-7 (IL-7) is a cytokine known for its importance in T cell development and survival. How IL-7 shapes CD8 T cell responses during an acute viral infection is less understood. We had previously shown that IL-7 signaling deficient mice have reduced accumulation of influenza-specific CD8 T cells following influenza infection. We sought to determine whether IL-7 affects early CD8 T cell expansion in the mediastinal lymph node and effector function in the lungs. Using IL-7Rα signaling deficient mice, we show that IL-7 is required for a normal sized mediastinal lymph node and the early clonal expansion of influenza-specific CD8 T cells therein. We show that IL-7 plays a cell-intrinsic role in the accumulation of NP_366-374 and PA_224-233-specific CD8 T cells in the lymph node. We also found that IL-7 shapes terminal differentiation, degranulation and cytokine production to a greater extent in PA_224-233-specific than NP_366-374-specific CD8 T cells. We further demonstrate that IL-7 is induced in the lung tissue by viral infection and we characterize multiple cellular sources that contribute to IL-7 production. Our findings on IL-7 and its effects on lower respiratory diseases will be important for expanding the utility of therapeutics that are currently available.

SUBMITTER: Sheikh A

PROVIDER: S-EPMC8741933 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Selective dependence of H2-M3-restricted CD8 responses on IL-15.

Project description:We studied whether CD8 T cell responses that are mediated by unconventional MHC class Ib molecules are IL-15 dependent in mice. CD8(+) T cell responses to Listeria monocytogenes infection that are restricted by the MHC class Ib molecule H2-M3 decreased in the absence of IL-15, whereas other primary MHC class Ib- and MHC class Ia-restricted responses were IL-15 independent. This result was confirmed in MHC class Ia-deficient mice in which IL-15 deficiency also reduced H2-M3-restricted but not all CD8 T cell responses to L. monocytogenes. IL-15 deficiency did not affect proliferation or survival of responding H2-M3-restricted CD8(+) T cells, but IL-15 was necessary to detect H2-M3-restricted CD8(+) T cells in naive mice. This finding suggests that these CD8(+) T cells require IL-15 during development, but become IL-15 independent after activation. IL-15 was necessary for the survival of most class Ib-restricted CD8(+) T cells, starting at the mature thymocyte stage in naive mice, but does not affect a distinct CD44(low)/CD122(low) subpopulation. These data suggest that the nature of the selecting MHC class Ib molecule determines whether CD8(+) T cells acquire IL-15 dependence during thymic development.

| S-EPMC3294130 | biostudies-literature

CD8+ Treg cells suppress CD8+ T cell-responses by IL-10-dependent mechanism during H5N1 influenza virus infection.

Project description:Although Treg-cell-mediated suppression during infection or autoimmunity has been described, functions of Treg cells during highly pathogenic avian influenza virus infection remain poorly characterized. Here we found that in Foxp3-GFP transgenic mice, CD8(+) Foxp3(+) Treg cells, but not CD4(+) Foxp3(+) Treg cells, were remarkably induced during H5N1 infection. In addition to expressing CD25, the CD8(+) Foxp3(+) Treg cells showed a high level of GITR and produced IL-10. In an adoptive transfer model, CD8(+) Treg cells suppressed CD8(+) T-cell responses and promoted H5N1 virus infection, resulting in enhanced mortality and increased virus load in the lung. Furthermore, in vitro neutralization of IL-10 and studies with IL-10R-deficient mice in vitro and in vivo demonstrated an important role for IL-10 production in the capacity of CD8(+) Treg cells to inhibit CD8(+) T-cell responses. Our findings identify a previously unrecognized role of CD8(+) Treg cells in the negative regulation of CD8(+) T-cell responses and suggest that modulation of CD8(+) Treg cells may be a therapeutic strategy to control H5N1 viral infection.

| S-EPMC4165276 | biostudies-literature

Transcriptional responses of antigen-specific CD8 T cells after secondary influenza virus challenge

Project description:To evaluate the transcriptional responses of effector and memory virus-specific CD8 T cell subsets after primary and secondary influenza infection, we sorted subsets of FluNP 366-374/Db+ CD8+ T cells from the BAL, lung, and spleen at the peak of primary x31 influenza infection (day 10), resting memory (day 30), or 3 days after secondary PR8 influenza challenge (Day 30+3). Cells from the circulation were excluded from BAL and lung based on intravital labeling with anti-CD45. Memory cells from the lung were further separated in TRM and TEM subsets based on expression of CD69 at the day 30 and day 30+3 timepoints. Memory cells from the BAL were separated into long-term airway resident versus recently-recruited cells based on CD11a expression at the day 30 and days 30+3 timepoints. The results show that virus-specific BAL and lung TRM cells, but not lung TEM cells or spleen TEM cells, rapidly alter their transcriptional program and increase expression of effector molecules within 3 days of a secondary influenza challenge.

2024-02-15 | GSE247464 | GEO

Subset- and Antigen-Specific Effects of Treg on CD8+ T Cell Responses in Chronic HIV Infection.

Project description:We, and others, have reported that in the HIV-negative settings, regulatory CD4+CD25highFoxP3+ T cells (Treg) exert differential effects on CD8 subsets, and maintain the memory / effector CD8+ T cells balance, at least in part through the PD-1/PD-L1 pathway. Here we investigated Treg-mediated effects on CD8 responses in chronic HIV infection. As compared to Treg from HIV negative controls (Treg/HIV-), we show that Treg from HIV infected patients (Treg/HIV+) did not significantly inhibit polyclonal autologous CD8+ T cell function indicating either a defect in the suppressive capacity of Treg/HIV+ or a lack of sensitivity of effector T cells in HIV infection. Results showed that Treg/HIV+ inhibited significantly the IFN-γ expression of autologous CD8+ T cells stimulated with recall CMV/EBV/Flu (CEF) antigens, but did not inhibit HIV-Gag-specific CD8+ T cells. In cross-over cultures, we show that Treg/HIV- inhibited significantly the differentiation of either CEF- or Gag-specific CD8+ T cells from HIV infected patients. The expression of PD-1 and PD-L1 was higher on Gag-specific CD8+ T cells as compared to CEF-specific CD8+ T cells, and the expression of these markers did not change significantly after Treg depletion or co-culture with Treg/HIV-, unlike on CEF-specific CD8+ T cells. In summary, we show a defect of Treg/HIV+ in modulating both the differentiation and the expression of PD-1/PD-L1 molecules on HIV-specific CD8 T cells. Our results strongly suggest that this particular defect of Treg might contribute to the exhaustion of HIV-specific T cell responses.

| S-EPMC5102588 | biostudies-literature

Antigen-specific memory regulatory CD4+Foxp3+ T cells control memory responses to influenza virus infection.

Project description:Regulatory CD4(+)Foxp3(+) T cells (Tregs) are key regulators of inflammatory responses and control the magnitude of cellular immune responses to viral infections. However, little is known about how Tregs contribute to immune regulation during memory responses to previously encountered pathogens. In this study, we used MHC class II tetramers specific for the 311-325 peptide from influenza nucleoprotein (NP311-325/IA(b)) to track the Ag-specific Treg response to primary and secondary influenza virus infections. During secondary infections, Ag-specific memory Tregs showed accelerated accumulation in the lung-draining lymph node and lung parenchyma relative to a primary infection. Memory Tregs effectively controlled the in vitro proliferation of memory CD8(+) cells in an Ag-specific fashion that was MHC class II dependent. When memory Tregs were depleted before secondary infection, the magnitude of the Ag-specific memory CD8(+) T cell response was increased, as was pulmonary inflammation and airway cytokine/chemokine expression. Replacement of memory Tregs with naive Tregs failed to restore the regulation of the memory CD8 T cell response during secondary infection. Together, these data demonstrate the existence of a previously undescribed population of Ag-specific memory Tregs that shape the cellular immune response to secondary influenza virus challenges and offer an additional parameter to consider when determining the efficacy of vaccinations.

| S-EPMC3608733 | biostudies-literature

MHC-based detection of antigen-specific CD8+ T cell responses.

Project description:The hallmark of adaptive immunity is its ability to recognise a wide range of antigens and technologies that capture this diversity are therefore of substantial interest. New methods have recently been developed that allow the parallel analysis of T cell reactivity against vast numbers of different epitopes in limited biological material. These technologies are based on the joint binding of differentially labelled MHC multimers on the T cell surface, thereby providing each antigen-specific T cell population with a unique multicolour code. This strategy of 'combinatorial encoding' enables detection of many (at least 25) different T cell populations per sample and should be of broad value for both T cell epitope identification and immunomonitoring.

| S-EPMC2892606 | biostudies-literature

IL-15 ex vivo overcomes CD4+ T cell deficiency for the induction of human antigen-specific CD8+ T cell responses.

Project description:CD4(+) Th cells are important for the induction and maintenance of antigen-specific CD8(+) T cell function, so their loss or dysfunction in HIV-infected or cancer patients could reduce the patients' ability to control viral infection. Previous work in murine systems indicated that IL-15 codelivered with vaccines could overcome CD4(+) Th cell deficiency for induction of functionally efficient CD8(+) T cells and maintenance of viral-specific CTLs, but its efficacy in helping primary human CD8(+) T cell responses is unknown. In the present study, a peptide-pulsed, DC-based human coculture ex vivo system was used to study the role of IL-15 in overcoming CD4(+) Th deficiency to elicit CD8(+) T cell responses in CD4-depleted PBMCs from healthy individuals and PBMCs from HIV-1-infected patients. We found that IL-15 could overcome CD4(+) Th deficiency to induce primary and recall memory CD8(+) T cell responses in healthy individuals. Moreover, in CD4-deficient, HIV-1-infected patients with diminished CD8(+) T cell responses, IL-15 greatly enhanced CD8(+) T cell responses to alloantigen. These results suggest that IL-15 may be useful in the development of therapeutic and preventive vaccines against cancers and viral infections in patients defective in CD4(+) Th cell.

| S-EPMC3114597 | biostudies-literature

IL-4/IL-4 Ab complex enhances the accumulation of both antigen-specific and bystander CD8 T cells in mouse lungs infected with influenza A virus.

Project description:BackgroundUnlike conventional T cells, innate and virtual-memory CD8 T cells in naïve mice acquire their memory phenotypes and functions in the absence of antigenic encounters in a cytokine-dependent manner. The relevant cytokines include interleukin-4 (IL-4), type I interferon, and interleukin-15 (IL-15). Moreover, exogenous IL-4 can also induce de novo generation and/or expansion of the virtual-memory CD8 T cell population. In this study, we investigated whether exogenous IL-4 could enhance the immune response to a viral infection.ResultsIn vivo administration of IL-4 and an anti-IL-4 antibody complex (IL-4C) increased CXCR3 expression in both memory and naïve phenotype CD8 T cells in the absence of antigenic stimulation, and protected mice from lethal influenza infection. Flow cytometric analysis of lung-infiltrating immune cells on day 5 after virus infection revealed higher numbers of antigen-specific and bystander CD8 T cells in IL-4C-treated mice than in control mice. In particular, the bystander CD8 T cells were a naïve or evident memory phenotypes. Crucially, an anti-CXCR3 blocking antibody abrogated this IL-4C effect, reflecting that the increased accumulation of CD8 T cells in the lungs after IL-4C treatment is dependent on CXCR3.ConclusionsThese data demonstrate that exogenous IL-4C plays a protective role by enhancing CXCR3-dependent migration of CD8 T cells into influenza-infected lungs.

| S-EPMC10691054 | biostudies-literature

Extrinsic Acquisition of CD80 by Antigen-Specific CD8+ T Cells Regulates Their Recall Immune Responses to Acute Viral Infection.

Project description:CD80 is mainly expressed on Ag-presenting cells (APCs) as a costimulatory molecule but is also detected on T cells. However, the origin and physiological role of CD80 on CD8+ T cells remain unclear. In the present study, we demonstrated that effector and memory CD8+ T cells, but not naïve CD8+ T cells, displayed CD80 molecules on their surfaces after acute lymphocytic choriomeningitis virus infection. Using adoptive transfer of CD80-knockout (KO) CD8+ T cells into a wild type or CD80-KO recipient, we demonstrated that the effector CD8+ T cells displayed CD80 by both intrinsic expression and extrinsic acquisition, while memory CD8+ T cells displayed CD80 only by extrinsic acquisition. Interestingly, the extrinsic acquisition of CD80 by CD8+ T cells was observed only in the lymphoid organs but not in the periphery, indicating the trogocytosis of CD80 molecules via interaction between CD8+ T cells and APCs. We compared the recall immune responses by memory CD8+ T cells that either extrinsically acquired CD80 or were deficient in CD80, and found that CD80, presented by memory CD8+ T cells, played a role in limiting their expansion and IL-2 production upon exposure to secondary challenge. Our study presents the in vivo dynamics of the extrinsic acquisition of CD80 by Ag-specific CD8+ T cells and its role in the regulation of recall immune responses in memory CD8+ T cells.

| S-EPMC6722275 | biostudies-literature

Broad influenza-specific CD8+ T-cell responses in humanized mice vaccinated with influenza virus vaccines.

Project description:The development of novel human vaccines would be greatly facilitated by the development of in vivo models that permit preclinical analysis of human immune responses. Here, we show that nonobese diabetic severe combined immunodeficiency (NOD/SCID) beta(2) microglobulin(-/-) mice, engrafted with human CD34+ hematopoietic progenitors and further reconstituted with T cells, can mount specific immune responses against influenza virus vaccines. Live attenuated trivalent influenza virus vaccine induces expansion of CD8+ T cells specific to influenza matrix protein (FluM1) and nonstructural protein 1 in blood, spleen, and lungs. On ex vivo exposure to influenza antigens, antigen-specific CD8+ T cells produce IFN-gamma and express cell-surface CD107a. FluM1-specific CD8+ T cells can be also expanded in mice vaccinated with inactivated trivalent influenza virus vaccine. Expansion of antigen-specific CD8+ T cells is dependent on reconstitution of the human myeloid compartment. Thus, this humanized mouse model permits preclinical testing of vaccines designed to induce cellular immunity, including those against influenza virus. Furthermore, this work sets the stage for systematic analysis of the in vivo functions of human DCs. This, in turn, will allow a new approach to the rational design and preclinical testing of vaccines that cannot be tested in human volunteers.

| S-EPMC2572794 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data